Open-Label Extension Study of Trofinetide for Rett Syndrome

An Open-Label Extension Study of Continuing Treatment With Trofinetide for Rett Syndrome

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04776746

Enrollment

Registered

2021-03-02

Start date

2020-11-08

Completion date

2023-06-30

Last updated

2024-09-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rett Syndrome

Brief summary

To investigate the safety and tolerability of continued long-term treatment with oral trofinetide in girls and women with Rett syndrome

Interventions

DRUGtrofinetide

Study drug is administered twice a day for up to approximately 32 months. Doses may be taken orally or administered by gastrostomy (G) tube. The subject's assigned dose for this study will be the final dose from the antecedent study (ACP-2566-004).

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

5 Years to 21 Years

Healthy volunteers

Inclusion criteria

1. Has completed the EOT visit of the antecedent trofinetide Study ACP-2566-004 (i.e., has completed 40 weeks) 2. May benefit from continued treatment with open-label trofinetide in the judgment of the Investigator 3. Can still swallow the study medication provided as a liquid solution or can take it by gastrostomy tube 4. The subject's caregiver is English-speaking and has sufficient language skills to complete the caregiver assessments Childbearing Potential 5. Subjects of childbearing potential must abstain from sexual activity for the duration of the study and for at least 30 days thereafter. If a subject is sexually active or becomes sexually active during the study, she must use 2 clinically acceptable methods of contraception (e.g., oral, intrauterine device \[IUD\], diaphragm plus spermicide, injectable, transdermal or implantable contraception) for the duration of the study and for at least 30 days thereafter. Subject must not be pregnant or breastfeeding.

Exclusion criteria

1. Began treatment with growth hormone during the antecedent study 2. Began treatment with IGF-1 during the antecedent study 3. Began treatment with insulin during the antecedent study 4. Has developed a clinically significant cardiovascular, endocrine (such as hypo- or hyperthyroidism, Type 1 diabetes mellitus, or uncontrolled Type 2 diabetes mellitus), renal, hepatic, respiratory, or gastrointestinal disease (such as celiac disease or inflammatory bowel disease) 5. Subject is judged by the Investigator or the Medical Monitor to be inappropriate for the study due to AEs, medical condition, or noncompliance with investigational product or study procedures in the antecedent study 6. Has a clinically significant abnormality in vital signs at Baseline 7. Has an average QTcF interval of \>450 ms on the Baseline ECG performed before the first dose of trofinetide is given in the present study (i.e., the ECG performed at the EOT visit of the antecedent study) 8. Has developed a clinically significant ECG finding during the antecedent study Additional inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Patients With Treatment-emergent Adverse Events (TEAEs), With Serious Adverse Events (SAEs), and With Withdrawals Due to AEs	Mean study drug exposure was 426 days, corresponding to 1.2 years	Withdrawals due to AEs included both study drug discontinuation as well as study termination
Number (%) of Patients With Potentially Clinically Important Changes in ECG Post-baseline	Mean study drug exposure was 426 days, corresponding to 1.2 years	Potentially clinically significant ECG changes were defined as QTcF \>500 ms or QTcF change from baseline (CFB) of \>60 ms
Number (%) of Patients With Potentially Clinically Important Changes in Vital Signs Post-baseline	Mean study drug exposure was 426 days, corresponding to 1.2 years	Potentially clinically important changes from baseline in vital signs were defined as: Systolic blood pressure (SBP) ≥180 mmHg and increased ≥20 mmHg from baseline; SBP ≤90 mmHg and decreased ≥20 mmHg from baseline; Diastolic blood pressure (DBP) ≥105 mmHg and increased ≥15 mmHg from baseline; DBP ≤50 mmHg and decreased ≥15 mmHg from baseline; Pulse rate (PR) ≥120 bpm and increased ≥15 bpm from baseline; PR≤50 bpm and decreased ≥15 bpm from baseline. Baseline was the baseline value of previous study ACP-2566-003.
Number (%) of Patients With Potentially Clinically Important Changes in Body Weight Post-baseline	Mean study drug exposure was 426 days, corresponding to 1.2 years	Potentially clinically important changes from baseline in body weight were defined as: Weight increase ≥7% from baseline Weight decrease ≥7% from baseline
Number (%) of Patients With Potentially Clinically Important Changes in Laboratory Parameters Post-baseline	Mean study drug exposure was 426 days, corresponding to 1.2 years	Potentially clinically important changes in laboratory parameters were defined as: sodium ≤125 mmol/L; sodium ≥155 mmol/L; potassium ≤3.0 mmol/L ; potassium ≥5.5 mmol/L; chloride ≤85 mmol/L; chloride ≥120 mmol/L; calcium \<2.0 mmol/L; calcium \>2.75 mmol/L; blood urea nitrogen ≥10.71 mmol/L; creatinine \>1.5× upper limit of normal (ULN); uric acid ≥505.75 μmol/L; lactate dehydrogenase (LDH) ≥3×ULN; glucose ≤2.48 mmol/L; glucose ≥11 mmol/L; albumin ≤26 g/L; albumin ≥60 g/L; protein ≤50 g/L; protein ≥100 g/L; alanine transaminase (ALT) ≥3×ULN; aspartate transaminase (AST) ≥3×ULN; gamma glutamyl transferase (GGT) ≥3×ULN; alkaline phosphatase (ALP) ≥3×ULN; bilirubin ≥1.5×ULN

Countries

United States

Participant flow

Recruitment details

This was a multicenter, open-label, long-term study of trofinetide to monitor the safety and efficacy of continuing trofinetide therapy for patients who previously completed a Phase 3 trofinetide study. Patients who completed the preceding open-label study ACP-2566-004 were eligible to enroll in this study. Study ACP-2566-004 was an extension study for randomized, double-blind, placebo-controlled study ACP-2566-003.

Participants by arm

Arm	Count
Trofinetide Trofinetide oral solution was administered twice daily for up to approximately 32 months, orally or administered by gastrostomy (G) tube. The patient's assigned dose for this study was the final dose from the antecedent study (ACP-2566-004).	77
Total	77

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	5
Overall Study	Death	4
Overall Study	Lack of Efficacy	3
Overall Study	Noncompliance with study drug	2
Overall Study	Not related to COVID-19	2
Overall Study	Study terminated by sponsor	61

Baseline characteristics

Characteristic	Trofinetide
Age, Continuous	12.0 years STANDARD_DEVIATION 4.38
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	1 Participants
Race (NIH/OMB) Black or African American	1 Participants
Race (NIH/OMB) More than one race	4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	71 Participants
Region of Enrollment United States	77 Participants
Sex: Female, Male Female	77 Participants
Sex: Female, Male Male	0 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	4 / 77
other Total, other adverse events	57 / 77
serious Total, serious adverse events	23 / 77

Outcome results

Primary

Number (%) of Patients With Potentially Clinically Important Changes in Body Weight Post-baseline

Potentially clinically important changes from baseline in body weight were defined as: Weight increase ≥7% from baseline Weight decrease ≥7% from baseline